FT011, Direct Targeting Fibrosis Improves Heart Function ...



DIRECTLY TARGETING MYOCARDIAL FIBROSIS WITH FT011 IMPROVES HEART FUNCTION IN EXPERIMENTAL DIABETIC CARDIAC DISEASE

Y. Zhang1, K. Connelly1,2, H. Krum3, R.E. Gilbert2, D.J. Kelly1

1University of Melbourne, Australia, 2University of Toronto, Canada, 3Monash University, Canada

Objective: The pathological accumulation of extracellular matrix is a key contributor to chronic heart failure in diabetes. The aim of this study was to test the efficacy of the novel anti-fibrotic drug, FT011 (Fibrotech Therapeutics Pty Ltd, Melbourne, Australia) in a rodent model of diabetic cardiomyopathy that develops cardiac dysfunction.

Methods: Male homozygous Ren-2 rats were randomized to streptozotocin or vehicle (n=8 per group). Diabetic and non-diabetic rats were further randomized to receive FT011 (200mg/kg/day) or vehicle for 6 weeks. Prior to tissue collection, animals underwent echocardiography and cardiac catheterization. Total collagen deposition and cardiomyocyte hypertrophy were assessed by picrosirius red and H & E staining, respectively.

Results: At 6 weeks, diabetic animals developed cardiac dysfunction associated with cardiac fibrosis. FT011 treated diabetic rats had significantly reduced interstitial fibrosis along with improvement of heart function (Table).

|Group |Myocardial |Cardiomyocyte area |EF (%) |End diastolic |End diastolic |PRSW |EDPVR |

| |fibrosis |(um2) | |volume |pressure (mmHg) | | |

| |(%/ area) | | |(ul) | | | |

|Control |1.88(0.44 |714(28 |80(1.4 |263(14.6 |4.62(0.51 |105(15 |0.025(0.004 |

|Control+FT011|1.6(0.24 |647(62 |82(1.2 |278(39.3 |4.44(0.77 |108(12 |0.024(0.003 |

|Diabetes |5.09(1.28* |882(38* |75(1.1* |320(18* |10.05(0.9* |44(6.6* |0.059(0.011* |

|Diabetic+FT01|2.42(0.43# |659(28# |83(1.2# |235(13.6# |7.92(1.49# |77(6.3# |0.020(0.003# |

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